The immune response to infection is mounted at several levels, not only in terms of distinct effector subtypes, but also in terms of anatomy. While much is known regarding the dynamics of the immune response in secondary lymphoid tissue our knowledge is rudimentary with respect to the workings of the immune system in non-lymphoid tissues. Learning the parameters for induction and control of the response in these sites is critical to our ability to understand immunity and manipulate vaccination, since a rapid response mediated by effector or memory-effector T cells in non-lymphoid tissues could be the defining event in the prevention of infectious disease. Therefore, this proposal is focused on determining the consequences of bacterial and viral infections on the primary and memory CD4 and CD8 T cell immune response in non-lymphoid tissues. Using techniques which allow sensitive detection of effector function these studies will provide a comprehensive picture of the immune response throughout the body. Our preliminary results suggest that subsets of antimicrobial effector and memory T cells are generated which display unique functional attributes in non-lymphoid versus lymphoid tissue and our goal is to analyze these differences in detail. The specific aims of this proposal are: 1. To analyze the basis for compartmentalization of effector function of CD8 memory T cells in non-lymphoid tissues. 2. To determine whether antimicrobial effector and memory CD4 T cells exhibit distinct functional abilities in lymphoid versus non-lymphoid tissues. 3. To determine the requirements for generation of CD4 T cell help in antimicrobial CD8 T cell responses.